Evidence map›Paper›PMID 32723475›Full record

ArticleeLife2020

A mechanism for the extension and unfolding of parallel telomeric G-quadruplexes by human telomerase at single-molecule resolution.

Bishnu P Paudel, Aaron Lavel Moye, Hala Abou Assi, Roberto El-Khoury, Scott B Cohen, Jessica K Holien, Monica L Birrento, Siritron Samosorn, Kamthorn Intharapichai, Christopher G Tomlinson and 6 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 54 citations in OpenAlex.

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  15. Telomerase structural biology comes of age.Current opinion in structural biology · 2022
    Review
  16. Review
  17. Review
  18. Triazolyl Dibenzo[Asian journal of organic chemistry · 2021
    Article
  19. Review
  20. G-quadruplex DNA: a novel target for drug design.Cellular and molecular life sciences : CMLS · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 9 institutions in 7 countries.

Bishnu P Paudel *Molecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, Australia.ORCID 0000-0003-3518-3882
Aaron Lavel Moye *Children's Medical Research Institute, University of Sydney, Westmead, Australia.
Hala Abou AssiDepartment of Chemistry, McGill University, Montreal, Canada.ORCID 0000-0003-1087-8805
Roberto El-KhouryDepartment of Chemistry, McGill University, Montreal, Canada.ORCID 0000-0002-8068-4566
Scott B CohenChildren's Medical Research Institute, University of Sydney, Westmead, Australia.
Jessica K HolienSchool of Science, College of Science, Engineering and Health, RMIT University, Melbourne, Australia.ORCID 0000-0002-8735-2871
Monica L BirrentoMolecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, Australia.
Siritron SamosornDepartment of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Srinakharinwirot University, Bangkok, Thailand.
Kamthorn IntharapichaiDepartment of Biobased Materials Science, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, Japan.
Christopher G TomlinsonChildren's Medical Research Institute, University of Sydney, Westmead, Australia.
Marie-Paule Teulade-FichouInstitut Curie, PSL Research University, Orsay, France.
Carlos GonzálezInstituto de Química Física 'Rocasolano', CSIC, Madrid, Spain.ORCID 0000-0001-8796-1282
Jennifer L BeckMolecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, Australia.
Masad J DamhaDepartment of Chemistry, McGill University, Montreal, Canada.ORCID 0000-0002-4458-1623
Antoine M van OijenMolecular Horizons and School of Chemistry and Molecular Bioscience, University of Wollongong, Wollongong, Australia.ORCID 0000-0002-1794-5161
Tracy M BryanChildren's Medical Research Institute, University of Sydney, Westmead, Australia.ORCID 0000-0002-7990-5501
University of Wollongong · AUMcGill University · CAThe University of Sydney · AUBoston Children's Hospital · USInstituto de Química Física Blas Cabrera · ESKyoto Institute of Technology · JPRMIT University · AUSrinakharinwirot University · THUniversité Paris-Sud · FR

Funding

Australian Research Council FL140100027Cancer Council NSW RG 11-07Cancer Council NSW RG 11-07,RG 16-10Cancer Council NSW RG 16-10Centre of Excellence for Innovation in Chemistry PERCH-CICResearch Unit of Natural Products and Organic Synthesis for Drug Discovery NPOS 405/2560
6 · The paper itself

Abstract

Telomeric G-quadruplexes (G4) were long believed to form a protective structure at telomeres, preventing their extension by the ribonucleoprotein telomerase. Contrary to this belief, we have previously demonstrated that parallel-stranded conformations of telomeric G4 can be extended by human and ciliate telomerase. However, a mechanistic understanding of the interaction of telomerase with structured DNA remained elusive. Here, we use single-molecule fluorescence resonance energy transfer (smFRET) microscopy and bulk-phase enzymology to propose a mechanism for the resolution and extension of parallel G4 by telomerase. Binding is initiated by the RNA template of telomerase interacting with the G-quadruplex; nucleotide addition then proceeds to the end of the RNA template. It is only through the large conformational change of translocation following synthesis that the G-quadruplex structure is completely unfolded to a linear product. Surprisingly, parallel G4 stabilization with either small molecule ligands or by chemical modification does not always inhibit G4 unfolding and extension by telomerase. These data reveal that telomerase is a parallel G-quadruplex resolvase.

Indexed as

G-QuadruplexesFluorescence Resonance Energy TransferHEK293 CellsHumansLigandsNanotechnologyNucleic Acid ConformationProtein BindingRNATelomeraseLigandsRNATelomerasebiochemistrychemical biologychromosomesgene expressionG-quadruplexhumantelomerasetelomere

Identifiers

PMID32723475
PMCPMC7426096
OpenAlexW3045625371

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.